The present invention is directed to medical methods and compositions for treatment of pain, in particularly acid-induced pain.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, for example, which may result from damage to body tissue, for example in general medical illnesses, cancer, neuropathies, and perioperative conditions. Pain may also be associated with medical disorders without a known cause, such as migraine and psychosomatic illness.
It is known Substance P (SP) is an undecapeptide belonging to the tachykinin small peptide family. SP is a pain neurotransmitter that helps excite and transmit pain signals from neural cells in many organs. Substance P is an important element in pain perception. The sensory function of substance P is thought to be related to the transmission of pain information into the central nervous system. Substance P coexists with the excitatory neurotransmitter glutamate in primary afferents that respond to painful stimulation. (De Felipe et al., Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature 392 (6674): 394-397, March 1998.) High levels of SP in muscle tissues and spinal fluid are frequently associated with chronic muscle pain such as myofascial pain syndrome and fibromyalgia, but the role of SP in muscle pain transmission and perception was unclear.
It was disclosed by Lin et al. that SP is an antinociceptive role in acid-induced chronic muscle pain. Lin showed that a single i.m. acid injection in mice lacking SP signaling by deletion of the tachykinin precursor 1 (Tac1) gene or coadministration of NK1 receptor antagonists produced long-lasting hyperalgesia rather than the transient hyperalgesia seen in control animals, and the inhibitory effect of SP was found exclusively in neurons expressing acid-sensing ion channel 3, where SP enhanced M-channel-like potassium currents through the NK1 receptor in a G protein-independent but tyrosine kinase-dependent manner. Furthermore, the SP signaling could alter action potential thresholds and modulate the expression of TTX-resistant sodium currents in medium-sized muscle nociceptor. (Lin et al., An antinociceptive role for substance P in acid-induced chronic muscle pain. PNAS 109 (2): E76-E83, January 2012.)
It is still desirable to develop a method or pharmaceutical composition for treating or managing pain.